The “Hallmarks of Cancer” paper by Douglas Hanahan and Robert Weinberg is a classic, and a must read (allow plenty of time) for anyone interested in cancer drug development.
The original 2000 paper, updated in 2011, identified six hallmarks of cancer, “distinctive and complementary capabilities that enable tumour growth and metastatic dissemination:”
- Sustaining Proliferative Signaling
- Evading Growth Suppressors
- Activating Invasion and Metastasis
- Enabling Replicative Immortality
- Inducing Angiogenesis
- Resisting Cell Death
Apoptosis or programmed cell death according to Hanahan and Weinberg is “a natural barrier to cancer development.” One of the ways cancer cells survive is by resisting cell death and disrupting the apoptosis signaling pathway; in other words the normal signals that trigger cell death don’t get through.
Researchers have shown that apoptosis is controlled at the cellular level, in the mitochondrion, by the Bcl-2 family of regulatory proteins (BCL-2, BCL-XL). Targeting BCL-2 (a protein that prevents apoptosis) could induce cell death and be a potentially successful anti-cancer strategy.
The result of our increased understanding of cancer biology has been the development of novel targeted drugs such as ABT-199, a potent and selective BCL-2 inhibitor. This is in early clinical development by AbbVie ($ABBV), a new biopharmaceutical company spun off from Abbott Laboratores ($ABT) last week.